Method of production of hydroxyaryl thioethers from sulfonium compounds

ABSTRACT

HYDROXYARYL THIOETHERS ARE PREPARED BY FIRST PREPARING A PHENYL SULFONIUM BISULFATE - EITHER DIRECTLY BY REACTING A PHENOL WITH DIMETHYL SULFOXIDE IN SULFURIC ACID OR STEPWISE BY REACTING AN ORGANIC SULFIDE WITH CHLORINE IN SULFURIC ACID TO FORM A CHLORO-SULFONIUM BISULFATE AND REACTING THIS CRUDE REACTION MIXTURE WITH A PHENOL - THEN REACTING THE CRUDE REACTION MIXTURE CONTAINING THE PHENYL SULFONIUM BISULFATE WITH WATER CONTAINING HALIDE IONS TO EFFECT FORMATION OF THE THIOETHER. NITRATION OF THE INTERMEDIATE PHENYL SULFONIUM BISULFATE THUS PREPARED CAN BE EFFECTED USING NITRIC ACID AND OPTIONALLY ADDITIONAL SULFURIC ACID WITHOUT THE ISOLATING OF ANY INTERMEDIATE PRODUCTS. NOVEL INTERMEDIATES ARE ALSO PREPARED VIA THIS METHOD.

United States Patent US. 01. 260-609 F 3 Claims ABSTRACT OF THEDISCLOSURE Hydroxyaryl thioethers are prepared by first preparing aphenyl sulfonium bisulfateeither directly by reacting a phenol withdimethyl sulfoxide in sulfuric acid or stepwise by reacting an organicsulfide with chlorine in sulfuric acid to form a chloro-sulfoniumbisulfate and reacting this crude reaction mixture with a phenol-thenreacting the crude reaction mixture containing the phenyl sulfoniumbisulfate with water containing halide ions to effect formation of thethioether. Nitration of the intermediate phenyl sulfonium bisulfate thusprepared can be effected using nitric acid and optionally additionalsulfuric acid without the isolating of any intermediate products. Novelintermediates are also prepared via this method.

This is a division of application Ser. No. 72,163, filed Sept. 14, 1970,now US. Pat. 3,732,317.

BACKGROUND OF THE INVENTION Scope of the invention Hydroxyarylthioethers have numerous uses some of which are described in US. Pat.3,282,979 and US. Pat. 3,274,257. In addition to those uses thesecompounds are valuable as intermediates in the preparation ofbiologically active agents such as herbicides. The intermediatesulfonium salts prepared according to this process find uses similar tothose described in US. Pat. 3,259,660, but are particularly useful asintermediates in the preparation of herbicidally active compounds.

This process provides an economical and eflicient means of producinghydroxyaryl thioethers and intermediate sulfonium salts. The process canbe easily employed on a commercial scale and utilizes inexpensive basicraw materials. The method first involves the formation of a phenylsulfonium bisulfate by one of two means. The first entails reacting anorganic sulfide with chlorine in the presence of sulfuric acid to form achloro-sulfonium bisulfate, which, in turn, is reacted with ahydroxyaryl compound to form the phenyl sulfonium bisulfate. In thesecond method, dimethyl sulfoxide is allowed to react with a hydroxyarylcompound in the presence of sulfuric acid to form the phenyl sulfoniumbisulfate. The crude reaction mixture prepared by either of these meansis then allowed to react with water containing halide ions to effectdecomposition and formation of the thioether. The use of sulfuric acidas a diluent and reactant in this process allows nitration of thearomatic moiety of the phenyl sulfonium bisulfate to be effected usingnitric acid and optionally sulfuric acid without isolating theintermediate phenyl sulfonium bisulfate. An important advantage of thisprocice ess is that in none of these steps do the intermediate productsneed to be isolated before proceeding to the next step.

Prior art The preparationof hydroxyaryl sulfonium chlorides has beendiscussed at length in US. Pat. 3,133,971 which discloses a process forpreparing hydroxyaryl sulfonium chlorides by reacting a mixture of anorganic thioether and a hydroxyaryl compound with chlorine, with orwithout an inert solvent system. US. Pat. 3,259,660 teaches thathydroxyaryl sulfonium chlorides can be prepared by reacting an organicthioether with chlorine either neat or, more effectively, in an inertsolvent, then reacting the resulting crude reaction product with aphenol to form the desired sulfonium chloride. If it is desired tonitrate the aromatic portion of the hydroxyaryl sulfonium chlorideformed in this manner, which utilizes an inert solvent, it is necessaryto perform the rather cumbersome procedure of isolating the salt byprecipitating and filtering before nitration of the ring can effectivelytake place. However, by reacting a sulfide and chlorine according to themethod of this invention in the presence of sulfuric acid, to form achlorosulfoniurn bisulfate which is then reacted with a phenol, a phenylsulfonium bisulfate is prepared, which can then be nitrated directly asthe crude reaction mixture without the intermediate step of isolatingthe phenyl sulfonium bisulfate. All that has to be done to effect thenitration is to mix nitric acid, and optionally sulfuric acid, with thecrude reaction product obtained according to this invention. The factthat nitration of the ring can be carried out without isolation of thesulfonium salt makes this process extremely valuable for incorporationinto other reaction schemes, such as the preparation of nitratedthioanisoles and derivatives thereof.

Prior art also teaches that in the production of 3-nitro- 4-halophenylethers from a sulfonium salt it is necessary to react the sulfonium saltwith perchloric acid (US. Pat. 3,159,683), or an aromatic sulfonic acid(US. Pat. 3,318,- 958), to form a salt which can be isolated thendecomposed to form the thioether.

It is also generally known in the art that hydroxyaryl sulfoniumperchlorates and sulfonates can be decomposed by refluxing in an aqueoussalt solution.

SUMMARY OF THE INVENTION It has now been discovered that hydroxyarylthioethers can be inexpensively and easily prepared by the processindicated below: (The meanings of the symbols used are set out hereafterin the Preferred Embodiment section of this patent application.)

(a) Reacting an organic sulfide of the Formula RS-R' with chlorine inthe presence of sulfuric acid, to form chloro-sulfonium bisulfate of theformula (b) Reacting the resulting reaction mixture with a hydroxyarylcompound to form the corresponding phenyl sulfonium bisulfate of thestructure:

(c) Reacting the resulting reaction mixture containing the phenylsulfonium bisulfate with an aqueous solution containing halide ions todecompose the sulfonium salt and form the corresponding sulfide.

Alternatively, steps (a) and (b) may be replaced by the following step:

(d) Reacting dimethylsulfoxide with a hydroxyaryl compound in thepresence of sulfuric acid to form a phenyl dimethylsulfonium bisulfate.

If it is desired that the final product obtained by use of this processbe a nitrated hydroxyaryl thioether, the crude recation mixture fromstep (b) or (d), above, can be allowed to react with nitric acid andoptionally additional sulfuric acid. Since sulfuric acid is a reactantand diluent in steps (a) and (d) and does not interfere with thenitration reaction (indeed, it is sometimes necessary for the nitrationreaction to be effected), the phenyl sulfonium bisulfate does not haveto be isolated before nitration will take place. In addition tonitrating phenyl sulfonium bisulfates, phenyl sulfonium halides can benitrated by means of the process of this invention as well. Atfer thenitration reaction, the resulting reaction mixture (again, no isolationof the nirated phenyl sulfonium bisulfate) is allowed to react asdescribed in step (c) above, to form the nitrated hydroxyaryl thioether.

The following nitrated phenyl sulfonium bisulfate formed according tothe process of this invention is novel:

HO R

5 -s ea H3049 R"... R The process of this invention is an economical andefficient method for making the intermediate sulfonium bisulfate andhydroxyaryl thioethers and is easily adaptable to commercial scale. Animportant advantage is that none of the intermediate products have to beisolated before continuing on to the next step; hence, it is unnecessaryto convert the phenyl sulfonium bisulfates to another form, such as aperchlorate, in order to isolate it before decomposing it to form thehydroxyaryl thioether.

The use of sulfuric acid as a diluent in the step (a) of the process ofthis invention results in the formation of a chloro-sulfonium bisulfateof the formula Thus far it has been extremely difiicult to isolate thisproduct and as yet it has not been done. It has been found, however,that the solutions of this chlorosulfonium bisulfate in sulfuric acidare thermally stable below 25 C. This stability is surprising in view ofthe instability of the analogous chloro-sulfonium chloride, of theformula as disclosed in US. Pat. 3,259,660. In that patent it is saidthat due to such a products relative instability at a. temperaturehigher than 0 C. which may lead to its hydrolysis to dimethyl sulfoxideor rearrangement to monochlorosulfide, it is preferable to react thisadduct with the phenol a relatively short time after the adduct isprepared. Because a sulfuric acid solution of the chlorosulfoniumbisulfate prepared according to the process of this invention isthermally stable at temperatures up to 25 C., it is not necessary tocarry out the second stage of this process leading to the formation ofthe phenyl sulfonium bisulfate immediately after the chloro-sulfoniumbisulfate has been prepared.

Similarly, the phenyl sulfonium bisulfate, prepared according to step(b) or (d) of the process of this invention, has also been extremelydifiicult to isolate, but, as in the case of the chloro-sulfoniumbisulfate, above, a sulfuric acid solution of this product is alsothermally stable, but in this case, at temperatures up to at least 50 C.

The stability of sulfuric acid solutions of these two intermediatesoffers certain operational advantages. For example, because of thisstability the necessity of running step (b) immediately subsequent tothe formation of the chloro-sulfonium bisulfate or of performing thenitration step immediately following the formation of the phenylsulfonium bisulfate is obviated. Thus, on a commercial scale, thisstability would allow operational difiiculties such as a plant shutdownto be overcome without having to take special precautions to prevent thedecomposition of the intermediates. For example, the chloro-sulfoniumbisulfate formed in the first step can be produced and stored if thepreparation of the phenyl-sulfonium bisulfate is delayed for somereason. Similarly, the phenyl-sulfonium bisulfate can be produced andstored if for some reason the next step of the reaction sequence istemporarily held up. After facilities are ready again, the intermediatescan be utilized in their respective reactions. These advantages are evenmore attractive in light of the fact that the sulfuric acid solutions ofthe chloro-sulfonium bisulfate and phenyl-sulfonium bisulfate do nothave to be treated or isolated from the crude reaction mixture. It willbe appreciated, however, that since the phenylsulfonium bisulfatesolution is more stable at higher temperatures than thechloro-sulfonium-bisulfate solution, it is preferable to prepare andstore a sulfuric acid solution of the former rather than the latter in asituation which forces storage of one or the other.

The evolution of hydrogen chloride gas in steps (a) and (b) of theprocess of this invention offers two advantages: (1) this gas is areadily available source of chloride ions which can be used in thedecomposition step to effect the formation of the thioether; (2) sincethe gas is relatively insoluble in sulfuric acid, the evolution of thegas assists in the removal of heat from the reactions, effectivelydecreasing the exothermicity of the reactions.

DESCRIPTION OF THE PREFERRED EMBODIMENTS The process of this inventionis carried out by first reacting an organic sulfide with chlorine in thepresence of sulfuric acid to form a chloro-sulfonium bisulfate, which inturn is reacted with a hydroxyaryl compound (a phenol) to form a phenylsulfonium. The phenyl sulfonium bisulfate is then decomposed byrefluxing in water containing a halide ion to form a hydroxyarylthioether. If a nitrated thioether is desired, the resulting mixturecontaining the phenyl sulfonium bisulfate is reacted with nitric acidand optionally additional sulfuric acid, and this resultant mixture thendecomposed by refluxing in water containing halide ions.

Generally, the organic sulfides suitable for use in the first reactionof this process comprise those having the general formula RSR', whereinR and R are radicals selected from the group consisting of alkyl,halogenated alkyl, aryl, alkaryl, and aralkyl. Illustrative of suitablealkyl radicals are methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl,decyl, dodecyl, pentadecyl, and substituted derivatives thereof, such aschloroethyl, chloropropyl and the like; of aryl radicals are phenyl,naphthyl and substituted derivatives thereof such as halophenyl andcarbethoxyphenyl; of aralkyl radicals are benzyl, phenylethyl, andsubstituted derivatives thereof such as nitrophenylethyl; or alkaryl aremethylphenyl, ethylphenyl, dimethylphenyl, butylphenyl and substitutedderivatives thereof such as ethylbromophenyl. Especially suitable aredialkyl sulfides together containing from 2 to 10 carbon atoms such asdimethyl sulfide, diethyl sulfide, dipropyl sulfide, methyl ethylsulfide, methyl octyl sulfide, ethyl propyl sulfide, and the like. Thepreferred organic thioether is dimethyl sulfide.

Chlorine can be added to the liquid reaction mixture as a liquld or agas; preferably it is in the gaseous state. The reaction of the sulfidewith chlorine in the presence of sulfuric acid can be carried out in ahomogeneous liquid medium or in a heterogeneous liquid medium, such as aslurry. However, for reaction rate, heat transfer and handlingconsideration, it is preferable that the reaction medium be ahomogeneous liquid. The reaction proceeds according to the followingreaction:

The concentration of the sulfuric acid can vary from 80 to 100 percentby weight w.) or even fuming sul furic acid (up to 65% W. S in H 50without hindering the reaction. It is preferred, however, to use 90-100% w. sulfuric acid, whether nitration is to follow or not. To avoidproblems of a two-phase system, it is also advantageous to use enoughacid to keep the organic sulfide, hydroxyaryl compound and the resultingsulfonium salt in solution. The amount of sulfuric acid required will bedependent on the solubility of the intermediates, which is determinableby one skilled in the art. Another consideration is that the amount ofthe acid used should be sufficient to supply the bisulfate ion of thesulfonium salt. This will be a molar amount at least equal to that ofthe chlorine, and will preferably be in excess of that amount to insurea homogeneous reaction system. The 2 than required for the reaction withthe sulfide. The reaction is carried out in a suitable vessel equippedwith a means of agitation, addition facilities, a vent line, and coolingequipment. The mixture is allowed to react in a temperature range ofabout 25 C. to 25 C., preferablybetween -10 C. and +10 C. Depending onthe volume and nature of the reactants, feed rates, agitation and otherfactors, the time needed to complete the reaction may vary from severalminutes to 10 hours or more. However, in a batch process, the reactiontime of /2 hour to 5 hours is usually sufficient to complete thereaction. In general, the organic sulfide and chlorine are reacted instoichiometric amounts with sulfuric acid; that is, equivalent molaramounts of the sulfide, chlorine and sulfuric acid are required for theformation of the same molar amount of the corresponding chloro-sulfoniumbisulfate. To avoid undesirable side reactions in the first step, it isbest to employ a slight excess of the sulfide over the chlorine.Accordingly, the mole ratio of sulfide to chlorine Will be in excess of1:1 and may be as high as 3:1. Still higher ratios may be employed ifdesired, although no particular benefits result therefrom. To minimizerecovery problems, the preferred mole ratio of sulfide to chlorine isbetween 1.021 and 1.511. The reaction can be run at atmospheric orsuperatmospheric pressures.

As contemplated in this invention, a hydroxyaryl compound is an aromaticcompound containing at least one OH group substituted on the benzenering, and having at least one unsubstituted reactive position in thearomatic ring. Suitable for use in the process of this invention aresimple hydroxyaryl compounds, such as phenol and naphthol, orsubstituted phenols. Substituents may be hydroxy, alkoxy, alkyl,halogen, nitro, amino, cyano, carboxy, acyl, and acetamido. Illustrativeof suitable substituted phenols are cresols, xylenols, alkylphenols suchas ethylphenol, propylphenol, butylphenol and the like, naphthols,monohalophenols, dihalophenols, guaiacol, catechol, resorcinol,nitrophenols, dinitrophenols, cyanophenols, hydroxybenzoic acid,hydroxybenzaldehyde, hydroxybenzyl ethers such as hydroxybenzyl methylether, hydroxybenzyl ethyl ether, hydroxybenzyl butyl ether and thelike, and alkoxyphenols such as ethoxyphenol, propoxyphenol,butoxyphenol and the like. It will be appreciated that the unsubstitutedreactive position is ortho or para to the hydroxy group on the benzenering. Eminently suitable for use in this process are phenol and themonosubstituted phenols such as cresol, resorcinol, guaiacol,cyanophenol, chlorophenol and the like. Phenol is preferred.

After a substantial amount of the chloro-sulfonium bisulfate is formedin the first step, the resulting reaction mixture is mixed with thehydroxyaryl compound and reacted to form the sulfonium salt. Generally,the hydroxyaryl compound and the product from the first step will bereacted in stoichiometric amounts (equimolar). However, to avoidundesired side reactions in the nitration step, if it follows, thephenol should be reacted with the reaction mixture of the first step inamounts somewhat less than the theoretical molar yield of the adductformed in first step. If the nitration step is to follow, the mole ratioof the chloro-sulfonium bisulfate, based on chlorine, to the hydroxyarylcompound is preferably a little over 1.0:1, but may be as high as 2.0:1.Still higher ratios could be employed if desired, but no particularbenefit would result therefrom and, in addition, recovery problems areminimized with lower mole ratios. The preferred mole ratio range ofchlorosulfonium bisulfate, based on chlorine, to the hydroxyarylcompound is about 1.05:1 to :1. If, on the other hand, nitration of thephenolsulfonium bisulfate is not to follow, a molar excess of phenol canbe added with no adverse effect on the reaction. The mole ratio in thiscase may be from 1.0:1 to 2.021 or more with the preferred range being1.0:1 to 15:1.

The reaction mixture from the first step can be added to the phenol in adifferent vessel, or the phenol can be added directly to the reactionmixture. The phenol can be added in the molten state for ease ofhandling and mixing. If the phenol is added in the molten state,however, consideration will have to be given for removal of the heat,since the reaction will be taking place at low temperature and thattemperature will have to be maintained. It has been found that phenolcontaining up to 10% water can be advantageously employed in thisreaction. The advantages of using phenol containing about 10% Water isthat it is readily available commercially and is a liquid at ambienttemperatures, thus lending itself to easy handling. The water contentdoes not interfere with the reaction either. The phenol may be added atonce or at a controlled rate, the latter being preferable. This rate mayvary from five minutes to several hours, depending on the volume of thereactants, the efficiency of the cooling equipment, and other factors.The temperature of this step of the process is best carried out betweento 25 C., and preferably between l0 and 10 C., for a time suflicient toproduce a substantial amount of hydroxyaryl sulfonium salt. Depending onthe volume and nature of the reactants, feed rates, agitation, and otherfactors, this time may vary from a few minutes to 10 hours or more. Thereaction can be carried out at atmospheric or superatmosphericpressures.

Alternatively, the phenyl sulfonium bisulfate can be obtained byallowing dimethylsulfoxide to react with a phenol (of the type describedabove) in the presence of sulfuric acid. This results in the formationof a phenyl dimethylsulfonium bisulfate. The reaction can be carried outby adding dimethylsulfoxide and the phenol simul taneously to sulfuricacid or by mixing the phenol with the sulfuric acid, then adding thedimethylsulfoxide to the mixture. Because of the exothermicity of thereaction it is preferred that the dimethylsulfoxide be added at a rateat which the temperature can be controlled. The three reactants aregenerally allowed to react in stoichiometric quantities (equimolar).However, it is preferable to maintain an excess of sulfuric acid whichmay be a mole ratio of up to 20.021 or more of sulfuric acid to phenol.A mole ratio of acid to phenol of between 2.021 to 10:1 is preferred.The mole ratio of dimethylsulfoxide to phenol is slightly in excess of1.0:1 and may be as high as 2.0:1, especially if nitration of theresulting phenyl sulfonium bisulfate is to follow. If so, a ratiobetween 1.0:1 and 1.5 :1 is preferred. However, if nitration is not tofollow this step, the phenol can be in excess of the dimethylsulfoxide.The temperature at which the reaction can be carried out is between 25and 25 C., preferably between 10 and 10 C. The concentration of thesulfuric acid can vary from 80 to 100% w. or even fuming sulfuric acid(up to 65% W. in sulfuric acid), but it is preferred to use 90 to 100%w. sulfuric acid. The phenol used can bel 00% w. pure or can contain upto w. water. Since phenol containing about 10% w. water is readilyavailable commercially and is a liquid at ambient temperatures, for easeof handling, it is advantageous to use this material. Commerciallyavailable dimethylsulfoxide is suitable for use in this process.

The decomposition of the phenyl-sulfonium bisulfate formed by either ofthe above two methods to form a thioether is effected by mixing thecrude reaction mixture containing the sulfonium salt with watercontaining halide ions such as chloride, bromide or iodide, and allowingto react preferably at reflux temperature. Because of the low cost andready availability of sources thereof, the chloride ion is preferred.The chloride ions are available from several sources. A soluble saltsuch as sodium chloride, potassium chloride, and the like, is dissolvedin water, and the resultant solution is refluxed with the reactionmixture. Another source of a chloride ion is the hydrogen chloride gasevolved in the formation of the chloro-sulfonium bisulfate and itssubsequent reaction to the phenol according to the process of thisinvention. In the first step, since sulfuric acid is used as a diluentand coreactant, an equimolar amount of hydrogen chloride is evolved foreach mole of the chlorosulfonium bisulfate formed. In the second step,for each mole of the phenylsulfonium bisulfate that is formed, one moleof hydrogen chloride gas is evolved according to the reaction Thehydrogen chloride evolved is easily utilized as a source of the chlorideion needed for the decomposition step merely by dissolving the hydrogenchloride gas in the water to be used for refluxing. Still another sourceis merely commercial hydrochloric acid. The ratio of chloride ions tothe sulfonium salt may be as high as 10:1 or as low as 0.01:1, but it ispreferable to be between about 0.5:1 and 2.0:1. The volume of water usedcan vary from a volume equal to or less than that of the reactionmixture to 20 times or more the volume of the reaction mixture. However,a volume of water which will result in an overall sulfuric acidconcentration of 30-40% w. is preferred. The decomposition can becarried out at atmospheric or superatmospheric pressure.

A nitrated hydroxyaryl thioether can be obtained through the addition ofa nitration step which utilizes nitric acid and, optionally, additionalsulfuric acid to nitrate the phenyl sulfonium salt. The sulfonium moietyon the ring protects the sulfur from reacting, and the nitration of thering can proceed unhindered and at low temperatures. The cumbersomeprocess of isolating intermediate sulfonium salt is unnecessary sincesulfuric acid is used as a diluent and reactant in the process and doesnot hinder the nitration. The overall process is as follows: (1)formation of the phenyl sulfonium bisulfate as previously described, (2)nitration of the aromatic moiety of the phenyl sulfonium bisulfate, and(3) formation of the thioether as previously described. It should benoted that HS 0. H01 R19 phenyl sulfonium halides, in particularchlorides, can be nitrated as well as bisulfates, by this method.

The amount of nitric acid used in the nitration step will be dependenton the degree of nitration of the aromatic ring desired and thesubstituents on the ring. If mononitrated product is preferred, only 1mole of nitric acid will be required per mole of the sulfonium compound,if a dinitrated product is desired, 2 moles will be needed. Sincedinitration can occur quite readily, care must be taken to use no morethan the stoichiometric amount needed for mononitration if so desired.It may even be necessary to employ a slight excess of the sulfoniumcompound if the dinitrated compound is to be excluded completely. Ifdinitration is desired it is preferable to use a slight molar excess ofnitric acid to insure complete dinitration. Since trinitration will notbe a concern in this process because of the difliculty of attachment ofthe third nitro group, the mole ratio of nitric acid to hydroxyarylsulfonium bisulfate may be as high as 321, but 2.0:1 to 2.5:1 ispreferred. The yields of the nitrated phenyl sulfonium bisulfate aregood if 93100% w. or even fuming sulfuric acid is used, but best resultsoccur as long as the concentration of the sulfuric acid is between 93and 100% W. at the end of the nitration reaction. (Determination of theconcentration of the sulfuric acid is found by dividing the free 100% w.sulfuric acid by free 100% w. sulfuric acid plus the amount of waterpresent.) The free 100% w. sulfuric acid is defined as the total 100% w.sulfuric acid added to the system minus the amount utilized to form thephenyl sulfonium bisulfate. The concentration of the nitric acid mayvary from between 50% w. to 100% w., with the preferred concentrationbeing between w. to 95% W. The mole ratio of w. sulfuric acid to 100% W.nitric acid can be between 1.0:1 to 20:1; however, the range of between2.021 to 10:1 is preferred. The reaction temperature is maintained atbetween -10 and +70 C., with the preferred temperature range being about0 C. to 50 C. Depending on the volume and nature of the reactants, feedrates, agitation, and other factors, the time for the completion of thereaction may vary from a few minutes to 10 hours or more. This step canbe carried out at atmospheric or superatmopsheric pressures.

The formation of the phenyl sulfonium bisulfate can also be carried outby placing the sulfide, phenol and sulfuric acid in the reaction vessel,then adding the chlorine; however, higher yields result from firstreacting the sulfide with chloride in sulfuric acid to form thechloro-sulfonium bisulfate, then reacting this with the hydroxyarylcompound in sulfuric acid to form the phenyl sulfonium bisulfate.

The following examples are used to further explain this invention:

EXAMPLE I Preparation of 2-hydroxy-4-methylphenyl methyl sulfide 35grams (g.) of dimethyl sulfide were stirred and dissolved in milliliters(ml.) 96 percent by weight w.) sulfuric acid between 10 and 25 C. Thesolution was cooled to 0 C. and 35.5 g. of chlorine was introduced as agas below the surface of the solution over a period of a half hour whilethe solution was constantly stirred and the temperature was kept at 0 C.During this reaction HCl gas evolved. To the resulting mixture 50 g. ofliquid p-cresol was added in 30 minutes, again with constant stirring at0 C. Stirring was continued for another hour, while the mixture wasallowed to warm to the ambient temperature. Again HCl gas was evolvedduring this reaction. The mixture was then poured into a solution of g.sodium chloride in 800 g. water and boiled overnight. The organic layerwas separated from the aqueous phase and the aqueous layer was thenextracted with three 50 ml. portions of methylene chloride which werethen combined with the original organic phase. The combined organicphases were dried over sodium sulfate, and then were subjected todistillation under reduced pressure. 68.1 grams of product was obtainedwhich was confirmed by analysis to be 2-hydroxy-S-methylphenyl methylsulfide.

EXAMPLE II Preparation of 4-hydroxy-3,S-dinitrophenyl methyl sulfide 1.1moles of dimethyl sulfide were dissolved at C. in 220 ml. of 96% W.sulfuric acid and placed in a vessel equipped with a means of agitation,temperature indicator, addition funnel, cooling system, and vent line.Subsequently, 1.0 mole of chlorine gas was introduced below the surfaceof the solution at -15 to over a period of 45 minutes. The reactionmixture was stirred constantly throughout the reaction, which wasslightly exothermic. Hydrogen chloride gas (HCl) was evolved during thereaction. To the resulting clear solution, 0.87 mole melted phenol wasadded with stirring and cooling, over a 45-minute period. After about /aof the phenol was added, HCl again started to escape at a temperature of-10 to C. This resulting reaction mixture containing the 4-hydroxyphenyldimethyl sulfonium bisulfate was allowed to warm to about C. over atwo-hour period.

This solution was then cooled to 0 C. 240 ml. of 30% fuming sulfuricacid was added, whereupon the nitration was started by addition of amixture of 100 ml. of 90% w. nitric acid (2.25 moles) and 240 ml. 30%fuming sulfuric acid. During the addition (1.5 hours), the temperaturewas kept at 05 C. by external cooling. After the addition was complete,the mixture was stirred for one hour during which time the temperaturewas allowed to rise to 30 C. Subsequently the mixture was poured into3.5 liters of water which contained 700 g. of sodium chloride, and wasboiled for two hours. Before the sulfonium compound started to decomposeinto 4-hydroxy 3,5 dinitrophenyl methyl sulfide (Compound I) nitrogendioxide fumes were evolved. The resulting dark red oil which formedduring the refluxing crystallized upon cooling to room temperature.Filtration gave, after drying, 195.4 g. (0.852 mole) Compound I, meltingpoint 100103 C. (pure product 102103 C.) in a yield of 98% based onphenol.

EXAMPLE III Preparation of 4-hydroxy-3,S-dinitrophenyl dimethylsulfonium bisulfate 1.05 mole of dimethylsulfide was dissolved at 20 C.in 213 ml. of 96% w. sulfuric acid and placed in a vessel equipped witha means of agitation, temperature indicator, addition funnel, coolingsystem and vent line. Subsequently, 0.99 mole of chlorine gas wasintroduced below the surface of the solution at 5 to 0 C. over a periodof 30 minutes. The reaction mixture was stirred constantly throughoutthe reaction which was slightly exothermic and during which time HCl wasevolved. To this resulting clear solution 0.96 mole melted phenol wasadded over a 45 minute period, during which time the mixture was stirredand maintained by external cooling at 5 to 0 C. The resulting reactionmixture was allowed to warm to room temperature over a two-hour period.

The solution was then cooled to 0 C. 126 ml. of 65% fuming sulfuric acidwas added, whereupon the nitration was started by addition of 95 ml. of90% nitric acid (2.03 mole). The first mole was added at C. over a-minute period, the second mole between and C. for the same amount oftime. The reaction mixture was kept at 50 C. for another hour.

A sample was taken (36.0 g., 3.8% of total amount) and mixed with 100ml. methanol under external cooling. Subsequently 250 ml. diethyl etheris added after seeding the solution with seed crystals of 4-hydroxy3,5-dinitro- 10 phenyl dimethylsulfonium bisulfate. A pale yellowprecipitate is formed which was isolated by filtration. Yield: 12.0 g.(97.5% m. on phenol) M.P.: 170172 C. The material was identified byelemental analysis and independent synthesis as4-hydroxy-3,S-dinitrophenyl dimethyl sulfonium bisulfate.

EXAMPLE IV Preparation of 4-hydroxy-3,S-dinitrophenyl methyl sulfideusing dimethylsulfoxide 18.8 g. of phenol were stirred and partiallydissolved in 44 ml. of concentrated sulfuric acid at 0 C. (The phenoldid not dissolve completely at this temperature.) To this mixture 16.0g. of dimethylsulfoxide were added dropwise over a period of 15 minuteswhile the reaction mixture was stirred and cooled to maintain thetemperature at 0 C. The reaction mixture was then stirred for two hourswhile it warmed to room temperature. (Some small pieces of phenol werestill visible.) At this point the crude reaction mixture contained the4- hydroxyphenyl dimethylsulfonium bisulfate.

40 ml. of fuming sulfuric acid (33% w. S0 approximately 0.3 mole S0 wereadded to the reaction mixture, whereupon the temperature increased to 60C. After cooling the resulting mixture down to 0 C., a mixture of 20.5ml. of w. nitric acid and 40 ml. 30% w. fuming sulfuric acid was addeddropwise over a 30-minute period while the reaction mixture wasconstantly stirred and kept below 7 C. by external cooling. After thenitric acid/ sulfuric acid mixture was added, the resulting reactionmixture was stirred for another 30 minutes at 1020 C. then poured into700 ml. water to Which 300 g. of sodium chloride were then added. Thismixture was heated to boiling and refluxed for two hours.

The resulting mixture was comprised of an aqueous phase and an organicphase (a red oil). The mixture was allowed to cool to room temperatureovernight whereupon the red oil formed red crystals. The reactionmixture was extracted 3 times with ml. of chloroform and the chloroformextract was then dried over magnesium sulfate. The chloroform wasevaporated under vacuum and the resulting red crystals were analyzed bythin-layer chromatography to be pure 4-hydroxy-3,S-dinitrophenyl methylsulfide.

Following procedures similar to those indicated in Examples I-IV,similar hydroxyaryl thioethers or sulfonium bisulfates can be obtainedby using the organic sulfides previously mentioned, such as diethylsulfide, methyl ethyl sulfide, and the like, in place of dimethylsulfide. In place of the phenol and cresol can be substituted any of thehydroxyaryl compounds described heretofore in this specification.

We claim as our invention:

1. A process for the preparation of a nitrated hydroxyaryl thioetherwhich comprises (a) reacting a phenol-sulfonium salt of the formulawherein R and R are each independently alkyl, halogenated alkyl, aryl,alkaryl or aralkyl, R" is OH, halogen, or alkyl, m is an integer between0 and 2, inclusive, and X is halogen or bisulfate, with nitric acid inthe presence of sulfuric acid, and

(b) reacting the crude reaction mixture from (a) with an aqueoussolution containing halide ions to form the thioether of the formula HO2)n 1 1 wherein n is 1 or 2 and R, R" and m are as described above.

2. The process according to claim 1 wherein R and R are alkyl togethercontain from 2 to 10 carbon atoms, X is chlorine or bisulfate, R" isalkyl of l to 4 carbon atoms, In is 0 or 1 and the halide ions arechloride.

3. The process according to claim 2 wherein R and R are methyl, m is O,n is 2 and OH is attached para References Cited Wagner et aL: Syn. Org.Chem. (1953) pp. 147 and 753.

LEWIS GOTTS, Primary Examiner to the position at which the sulfur isattached to the ring. 10 D. R. PHILLIPS, Assistant Examiner

